Insulin-sensitizing effects of a novel α-methyl-α-phenoxylpropionate derivative in vitro

Aim:To examine the insulin sensitizing effects of a novel α-methyl-α-phenoxylpropionate derivative YY20 in insulin-sensitive cell lines.Methods:Theperoxisome proliferator-activated receptor γ(PPARγ)agonist bioactivities of YY20were detected by a preadipocyte differentiation assay.RT-PCR and Westernblotting analysis were used to detect the expression of the target gene or protein.The effects of YY20 on insulin-mediated glucose consumption were determined inthe HepG2 human hepatocellular carcinoma line.Results:YY20 could enhancethe differentiation of preadipocytes to adipocytes and upregulate the gene ex-pression of PPARγ2,as well as the protein expression of insulin receptor sub-strate-1(IRS-1),glucose transporter-4(GLUT4),and adiponectin(ACRP30).Theeffects on GLUT4 and ACRP30 could be reversed by the PPARγ inhibitor SR-202.Furthermore,YY20 efficiently reduced glucose consumptions in HepG2 cells after24 h culture,and the effects were related to insulin and YY20 concentrations.Conclusion:YY20,a potential insulin-sensitizing agent like rosiglitazone,couldenhance glucose consumption in HepG2 cells in a concentration-and insulin-dependent manner.It may improve the insulin resistance associated with type 2diabetes.